Phylogenetic analysis of mitochondrial DNA in Japanese pedigrees of sensorineural hearing loss associated with the A1555G mutation

Thirteen Japanese families (ten of which were from the northern part of Jap an), with sensorineural hearing loss associated with the 1555 A to G (A1555 G) mitochondrial mutation, a known cause of non-syndromic hearing loss, wer e phylogenetically analysed using data obtained by restriction fragment len gth polymorphism (RFLP) and D-loop sequencing of mitochondrial DNA (mtDNA). Various types of mtDNA polymorphism were detected by restriction enzymes a nd D-loop sequence. No common polymorphic pattern throughout the 13 familie s was found, though three families exhibited the same restriction patterns and the same sequence substitution in the D-loop. To find where each of the 13 families are situated in the phylogenetic tree, the 482-bp of D-loop se quence were compared with those of 62 normal Japanese subjects. Despite the three families mentioned above appearing to be clustered, the remaining 10 families were scattered along the phylogenetic tree. This indicates that t here was no common ancestor for the 13 Japanese families bearing the A1555G mutation except three families, and that the A1555G mutation occurred spor adically and multiplied through evolution of the mtDNA in Japan. The presen t results showed that the common pathogenicity (hearing loss associated wit h the A1555G mutation) can occur sporadically in families which have differ ent genetic backgrounds, even in the Japanese population.